학술논문
p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study
Document Type
article
Author
Martin Köbel; Eun‐Young Kang; Ashley Weir; Peter F Rambau; Cheng‐Han Lee; Gregg S Nelson; Prafull Ghatage; Nicola S Meagher; Marjorie J Riggan; Jennifer Alsop; Michael S Anglesio; Matthias W Beckmann; Christiani Bisinotto; Michelle Boisen; Jessica Boros; Alison H Brand; Angela Brooks‐Wilson; Michael E Carney; Penny Coulson; Madeleine Courtney‐Brooks; Kara L Cushing‐Haugen; Cezary Cybulski; Suha Deen; Mona A El‐Bahrawy; Esther Elishaev; Ramona Erber; Sian Fereday; AOCS Group; Anna Fischer; Simon A Gayther; Arantzazu Barquin‐Garcia; Aleksandra Gentry‐Maharaj; C Blake Gilks; Helena Gronwald; Marcel Grube; Paul R Harnett; Holly R Harris; Andreas D Hartkopf; Arndt Hartmann; Alexander Hein; Joy Hendley; Brenda Y Hernandez; Yajue Huang; Anna Jakubowska; Mercedes Jimenez‐Linan; Michael E Jones; Catherine J Kennedy; Tomasz Kluz; Jennifer M Koziak; Jaime Lesnock; Jenny Lester; Jan Lubiński; Teri A Longacre; Maria Lycke; Constantina Mateoiu; Bryan M McCauley; Valerie McGuire; Britta Ney; Alexander Olawaiye; Sandra Orsulic; Ana Osorio; Luis Paz‐Ares; Teresa Ramón y Cajal; Joseph H Rothstein; Matthias Ruebner; Minouk J Schoemaker; Mitul Shah; Raghwa Sharma; Mark E Sherman; Yurii B Shvetsov; Naveena Singh; Helen Steed; Sarah J Storr; Aline Talhouk; Nadia Traficante; Chen Wang; Alice S Whittemore; Martin Widschwendter; Lynne R Wilkens; Stacey J Winham; Javier Benitez; Andrew Berchuck; David D Bowtell; Francisco J Candido dos Reis; Ian Campbell; Linda S Cook; Anna DeFazio; Jennifer A Doherty; Peter A Fasching; Renée T Fortner; María J García; Marc T Goodman; Ellen L Goode; Jacek Gronwald; David G Huntsman; Beth Y Karlan; Linda E Kelemen; Stefan Kommoss; Nhu D Le; Stewart G Martin; Usha Menon; Francesmary Modugno; Paul DP Pharoah; Joellen M Schildkraut; Weiva Sieh; Annette Staebler; Karin Sundfeldt; Anthony J Swerdlow; Susan J Ramus; James D Brenton
Source
The Journal of Pathology: Clinical Research, Vol 9, Iss 3, Pp 208-222 (2023)
Subject
Language
English
ISSN
2056-4538
Abstract
Abstract Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high‐grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi‐institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36–3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11–2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC.